Highly active anti retroviral therapy (HAART) has dramatically improved life expectancy of human immunodeficiency virus (HIV) infected patients, converting HIV infection into a chronic illness with associated changes in its attendant renal complications. The past two decades have witnessed a decrease in the prevalence of HIV associated nephropathy (HIVAN), traditionally considered to be the hall mark of renal involvement in HIV infection. Simultaneously a host of other glomerular and tubulo-interstitial diseases have emerged, expanding the spectrum of HIV associated renal diseases, predominant among which is HIV associated immune complex mediated kidney diseases (HIVICK). Of the diverse glomerular diseases constituting HIVICK, fibrillary glomerulonephritis (FGN) remains a rarity, with only two existing reports to date, confined to patients co-infected with Hepatitis C virus (HCV). The pathogenetic role of HIV in these patients remains under a cloud because of previously well established association of HCV infection and FGN. We report a case of FGN in a HIV seropositive, HCV negative Indian patient, highlighting the diagnostic electron microscopy (EM) findings of FGN and strengthening the causal association of HIV with FGN. In view of increasing heterogeneity of renal complications in HIV infection, the diagnostic utility of a comprehensive renal biopsy evaluation inclusive of EM is emphasized for appropriate selection of treatment modalities.

With the advent of highly active antiretroviral therapy (HAART), the disease burden of renal involvement in human immunodeficiency virus (HIV)-infected patients is currently on the rise along with a parallel change in its profile. A wide spectrum of HIV-associated immune complex-mediated kidney disease (HIVICK) has been described of late, especially in Caucasian and Asian populations,[1],[2] in addition to classical HIV-associated nephropathy (HIVAN). HIVICK lesions with organized glomerular deposits are quite rare and mostly described in patients with concurrent seropositivity for hepatitis C virus (HCV).[3],[4] The causative role of HIV in such scenarios remains suspect. We report a case of fibrillary glomerulonephritis (FGN) in an HIV-positive but HCV-negative patient, emphasizing the role of renal biopsy with ultrastructural analysis in the diagnosis and management of HIV-infected patients with renal disease.

Case Report

A 46-year-old Indian male presented with bilateral pedal edema and weakness of 6-month duration. He gave a past history of being diagnosed with HIV infection, 9 years back, but had never taken HAART, opting for native/nonallopathic medical treatment at the time. He was not on follow-up till 2 months before current presentation when he developed pyrexia of unknown origin, weight loss, and anorexia for which he was initiated empirically on antituberculous treatment (ATT) with isoniazid, rifampicin, pyrazinamide, and ethambutol at his local medical center. However, ATT was discontinued after 5 days when he developed vomiting and was found to have transaminitis. He was referred to us for further management, on suspicion of ATT-induced hepatitis and background history of positive retroviral status.

ATT was restarted and liver function remained normal. One month later, he was started on HAART with abacavir, lamivudine, and efavirenz. Proteinuria was managed with losartan. At last follow-up, proteinuria was 2 g/day and serum creatinine was 0.9 mg/dL.

Discussion

The most common kidney lesion traditionally described in HIV-infected patients has been termed HIVAN presenting with rapidly progressive renal failure and proteinuria and diagnosed on renal biopsy which shows collapsing glomerulopathy and characteristic tubulointerstitial changes. For more than a decade, HIVAN was considered the prototype of renal involvement in HIV, obviating the need for renal biopsies to search for other causes of proteinuria and renal dysfunction in this population, particularly in low-resource settings. However, in the current era of HAART and increased longevity of HIV-infected patients, the profile of renal pathology in HIV infection has undergone a sea change, moving beyond classical HIVAN.[1],[2] While HIVAN still remains the most common HIV-driven kidney lesion in HAART naive patients of African descent, recent trends reveal a higher prevalence of HIVICK among Caucasians and Asians.[1],[2] Genetic susceptibility due to APOL1 polymorphisms, availability of HAART, and access to health-care systems may be responsible for this expanding renal pathological profile in HIV patients.[2]

The variety of lesions observed in HIVICK includes IgA nephropathy, membranoproliferative glomerulonephritis, membranous nephropathy, postinfectious glomerulonephritis, lupus-like glomerulonephritis, cryoglobulinemic glomerulonephritis, ITGN, and FGN.[1],[2] ITGN and FGN are uncommon glomerular diseases with immune deposits demonstrating organized substructure distinct from amyloid and cryoglobulins.[5] The association between ITGN/FGN and HCV infection is well recorded.[6] Only two cases of FGN associated with HIV infection have been reported to date, both of whom were coinfected with HCV,[3] rendering the pathogenic relationship to HIV unclear. Due to the heterogeneity of HIVICK lesions, contemporary renal research focuses on establishing causality and thereby optimizes immunosuppressive therapy of HIVICK in the already immunocompromised HIV-positive patient.[1] The present case of FGN occurring in a patient with HIV monoinfection whose renal symptoms responded to treatment for HIV infection is a valuable pointer to the causal role of HIV in this setting and also reinforces the value of HAART in managing HIVICK without additional cytotoxic therapies for immunosuppression.

Passive trapping of circulating immune complexes resulting from polyclonal hypergammaglobulinemia in HIV infection is the favored theory of pathogenesis of HIVICK and supported by the elegant demonstration of HIV antigens p24, gp41, and gp120 bound to IgG or IgA antibodies in circulating and tissue immune complexes in HIV-infected patients.[2] It is possible to speculate further on the physiochemical nature of the fibrillary deposits by analogous comparison to HCV-related FGN in which a “slow cryoglobulin” (not detectable by standard tests for cryoglobulins) with affinity for matrix proteins such as fibronectin has been postulated to form organized fibrils.[6]

This case illustrates the need to lower our threshold for performing renal biopsies in HIV-positive patients, in support of the “test and treat” policy advocated currently for HIV prevention and management.[1] A composite renal biopsy evaluation inclusive of ultrastructural analysis will go a long way toward expanding our knowledge on the epidemiology, pathogenesis, and optimal management of renal involvement in HIV.